Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration.
Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), and Dab1 are the main components of the Reelin signalling cascade. Reelin is the sole ligand defined so far in signalling through this pathway. Postnatal migration of neuronal precursors from the subventricular zone (SVZ) to the olfactory bulb (OB), however, depends on ApoER2 and Dab1, but functions independently of Reelin. Here, we show that thrombospondin-1 (THBS-1) is a novel physiological ligand for ApoER2 and VLDLR. THBS-1 is present in the SVZ and along the entire rostral migratory stream (RMS). It binds to ApoER2 and VLDLR and induces phosphorylation of Dab1. In contrast to Reelin, it does not induce Dab1 degradation or Akt phosphorylation, but stabilizes neuronal precursor chains derived from subventricular explants. Lack of THBS-1 results in anatomical abnormalities of the RMS and leads to a reduction of postnatal neuronal precursors entering the OB.
Blake
Sophia M
SM
Department of Medical Biochemistry, Max F Perutz Laboratories, Medical University Vienna, Vienna, Austria.
Strasser
Vera
V
Andrade
Nuno
N
Duit
Sarah
S
Hofbauer
Reinhold
R
Schneider
Wolfgang J
WJ
Nimpf
Johannes
J
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; D019700:Thrombospondin 1; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases